Aberrant methylation of human L- and M-fructose 1,6-bisphosphatase genes in cancer.
A possible epigenetic regulation of the two isoenzymes of fructose 1,6-bisphosphatase (FBPase) was studied in liver, muscle, mamma, breast cancer and in different cancer cell lines. Results obtained after bisulfite sequencing revealed a different CpG methylation of both promoters in liver, muscle and breast tissue which is putatively involved in the cell-type specific gene expression of the two enzymes. In tumor cell lines, demethylation with 5-aza-deoxycytidine activated the expression of both isoenzymes. Additional inhibition of histone deacetylase with trichostatin A further increased FBPase mRNA concentrations. Since cancers typically have an abnormal energy metabolism and exhibit a low gluconeogenic phenotype, it was studied whether promoter methylation contributes to the decreased expression of FBPase in breast cancer. When non-malignant and malignant tissue samples from the same patient were compared a correlation between an increase of FBPase promoter methylation and a decrease of FBPase mRNA levels was observed.
Bigl
Marina
M
Institute of Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany.
Jandrig
Burkhard
B
Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Horn
Lars-Christian
LC
Institute of Pathology, Division of Gynecologic and Perinatal Pathology, University of Leipzig, Leipzig, Germany.
Eschrich
Klaus
K
Institute of Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany. Electronic address: eschrich@uni-leipzig.de.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001374:Azacitidine / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects; D005260:Female; D006597:Fructose-Bisphosphatase / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008875:Middle Aged; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics; D011401:Promoter Regions, Genetic
D006877:Hydroxamic Acids; C012589:trichostatin A; D006597:Fructose-Bisphosphatase; D001374:Azacitidine